During the course of medical diagnosis, treatment, and the follow-up of various medical conditions, it is often necessary for the physician to block a certain blood vessel, deprive a certain area of life-sustaining blood, or fill a cavernous area in the blood vessel. For example, where a certain blood vessel is perforated, blood will flow out of the vessel into the local area causing a hemorrhage. For this condition, the physician will need to, inter alia, plug the perforation or occlude the vessel upstream of the perforation. In another example, where a tumor is located, one therapy for reducing the tumor or eliminating it completely is to occlude the vessel upstream of the tumor and deprive blood to the tumor. The tumor dies off. In both of these examples, a strategically placed thrombus or embolism completes the desired occlusion. However, the current state of technology requires man-made synthetic embolus, such as metal emboli, or other embolization-causing synthetic polymers. For example, polytetrafluoroethylene (PTFE) is a synthetic polymer often used in vascular graft prosthesis, but has been known to cause hyperplasia in the vessel. DACRON® material is another synthetic material often used in vivo vascular treatments, but like many synthetic materials, it can harbor microorganisms causing infection.
In the case of aneurysm treatment, an aneurysm is caused by a weakening of the vessel wall, which causes an invagination of the vessel wall. Blood flow is inhibited at the neck of the aneurysm due to turbulence caused by blood entering and exiting the lumen of the aneurysm. Current medical treatment of aneurysms include the use of metal coils, such as the FDA approved Gugliemi Detachable Coil, inserted into the lumen of the aneurysm. However, this platinum coil is relatively soft and does not provide a complete packing of the aneurysm lumen. It is not uncommon for the aneurysm to re-canalize, enlarge, and even rupture. Therefore, an aneurysm lumen filling device that packs the lumen sufficiently, is biocompatible, and promotes healing of the aneurysm would be well-received as reportedly approximately 28,000 patients suffer from intracranial aneurysms, of which 19,000 become severely disabled or die as a result of an aneurysm rupture. Furthermore, an embolization device that is soft enough to not puncture the vessel wall, yet strong enough to provide the necessary occlusion, are also desirable characteristics.
Tissue implants in a purified form and derived from collagen-based materials have been manufactured and disclosed in the literature. Cohesive films of high tensile strength have been manufactured using collagen molecules or collagen-based materials. Aldehydes, however, have been generally utilized to cross-link the collagen molecules to produce films having high tensile strengths. With these types of materials, the aldehydes can leech out of the film, e.g. upon hydrolysis. Because such residues are cytotoxic, the films are poor tissue implants.
Other techniques have been developed to produce collagen-based tissue implants while avoiding the problems associated with aldehyde cross-linked collagen molecules. One such technique is illustrated in U.S. Pat. No. 5,141,747 wherein the collagen molecules are cross-linked or coupled at their lysine epsilon amino groups followed by denaturing the coupled, and preferably modified, collagen molecules. The disclosed use of such collagen material is for tympanic membrane repair. While such membranes are disclosed to exhibit good physical properties and to be sterilized by subsequent processing, they are not capable of remodeling or generating cell growth or, in general, of promoting regrowth and healing of damaged or diseased tissue structures.
In general, researchers in the surgical arts have been working for many years to develop new techniques and materials for use as implants to replace or repair damaged or diseased tissue structures, for example, blood vessels, aneurysms, muscle, ligaments, tendons and the like. It is not uncommon today, for instance, for an orthopedic-surgeon to harvest a patellar tendon of autogenous or allogenous origin for use as a replacement for a torn cruciate ligament. The surgical methods for such techniques are known. Further, it has been common for surgeons to use implantable prostheses formed from plastic, metal and/or ceramic material for reconstruction or replacement of physiological structures. Yet, despite their wide use, surgical implanted prostheses present many attendant risks to the patient.
Researchers have also been attempting to develop satisfactory polymer or plastic materials to serve as such functional tissue structures and/or other connective tissues, e.g., those involved in hernia and joint dislocation injuries. It has been discovered that it is difficult to provide a tough, durable plastic material which is suitable for long term connective tissue replacement. The tissues surrounding the plastic material can become infected and difficulties in treating such infections often lead to the failure of the implant or prostheses.
As mentioned above, various collagen-based materials have also been utilized for the above-mentioned tissue replacements; however, these materials either did not exhibit the requisite tensile strength or also had problems with infection and other immunogenic responses, encapsulation, or had other problems. In a related patent, U.S. Pat. No. 5,372,821, it is disclosed that a submucosa collagen matrix can be sterilized by conventional techniques, e.g., aldehyde tanning, propylene oxide, gamma radiation and peracetic acid. No specific processing steps are disclosed except that the submucosa layer is first delaminated from the surrounding tissue prior to sterilization treatment.
Some materials considered desirable are biological materials (biomaterials) from autogenous, allogenous, or xenogeneic (heteroplastic) sources. Biomaterials are desirable as they can be malleable and less likely to be rejected as foreign. One such biomaterial is collagen. Collagen is protein molecule that comes in many types. For example, collagen type I constitutes a significant amount of the collagen in the body. Type I is a heterotrimeric molecule, has a helical configuration, and is characterized by a Glycine-X-Y amino acid repeating sequence. Due to its abundance in the human body, collagen is being examined for its uses in medical treatment. One such treatment is for plugging vascular holes caused by the withdrawal of a catheter from the vessel. The collagen plug is inserted into the remaining hole as the hole begins to close up. In this manner the collagen plug remains in the hole with the adjacent tissue holding it in place.